Peroxisome proliferator-activated receptor upregulates galectin-9 and predicts prognosis in intestinal-type gastric cancer
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- 作者：Soo-Jeong Cho ; Myeong-Cherl Kook ; Jun Ho Lee ; Ji-Young Shin ; JuRi Park ; Young-Ki Bae ; Il Ju Choi ; Keun Won Ryu and Young-Woo Kim
- 关键词：gastric cancer ; intestinal-type gastric cancer ; peroxisome proliferator-activated receptor (PPAR) ; galectin-9 ; prognosis ; survival
- 刊名：International Journal of Cancer
- 出版年：2015
- 出版时间：15 February, 2015
- 年：2015
- 卷：136
- 期：4
- 页码：810-820
- 全文大小：883K
- ISSN：1097-0215
文摘
The importance of PPAR (peroxisome proliferator-activated receptor ) in gastric cancer (GC) is unclear. We investigated the role of PPAR in GC cell lines and an animal model, and its prognostic significance of PPAR in GC patients. We controlled PPAR and galectin-9 expression by using siRNAs and lentiviral constructs. Interaction between PPAR and galectin-9 was evaluated using luciferase and chromatin immunoprecipitation assays. PPAR expression in GCs was determined by immunohistochemical staining of tissue microarrays and survival analysis was done. Overexpression of PPAR was accompanied by increased galectin-9. Enhanced PPAR or galectin-9 expression increased E-cadherin expression; decreased expression of N-cadherin, fibronectin, snail, twist and slug and reduced cell invasion and migration. PPAR bound to the galectin-9 promoter region. Galectin-9 activity increased in PPAR-overexpressing cells but decreased in PPAR siRNA-treated cells. In a zebrafish xenograft model, the number of migrated cancer cells and number of fish with AGS cells in the tail vein were reduced in PPAR-overexpressing GC cells. PPAR was expressed in 462 of the 688 patients (69.2%) with GC. In 306 patients with intestinal-type GC, those with PPAR-positive tumors had lower overall and cancer-specific mortalities than those with PPAR-negative tumors. PPAR expression was an independent prognostic factor for overall and GC-specific mortality in patients with intestinal-type GC (adjusted hazard ratio, 0.42; 95% CI, 0.22–0.81). PPAR inhibits cell invasion, migration and epithelial–mesenchymal transition through upregulation of galectin-9 in vitro and in vivo.